Using Cone Beam Computed Tomography for radiological assessment beyond dento-maxillofacial imaging: a review of the clinical applications in other anatomical districts

Background: Cone Beam Computed Tomography (CBCT) represents the optimal imaging solution for the evaluation of the maxillofacial and dental area when quantitative geometric and volumetric accuracy is necessary (e.g., in implantology and orthodontics). Moreover, in recent years, this technique has given excellent results for the imaging of lower and upper extremities. Therefore, significant interest has been increased in using CBCT to investigate larger and non-traditional anatomical districts. Objective: The purpose of this work is to review the scientific literature in Pubmed and Scopus on CBCT application beyond head districts by paying attention to image quality and radiological doses. Method: The search for keywords was conducted in Pubmed and Scopus databases with no back-date restriction. Papers on applications of CBCT to head were excluded from the present work. From each considered paper, parameters related to image quality and radiological dose were extracted. An overall qualitative evaluation of the results extracted from each issue was done by comparing the conclusive remarks of each author regarding doses and image quality. PRISMA statements were followed during this process. Results: The review retrieved 97 issues from 83 extracted papers; 46 issues presented a comparison between CBCT and Multi-Detector Computed Tomography (MDCT), and 51 reviewed only CBCT. The radiological doses given to the patient with CBCT were considered acceptable in 91% of cases, and the final image quality was found in 99%. Conclusion: CBCT represents a promising technology not only for imaging of the head and upper and lower extremities but for all the orthopedic districts. Moreover, the application of CBCT derived from C-arms (without the possibility of a 360 ° rotation range) during invasive investigations demonstrates the feasibility of this technique for non-standard anatomical areas, from soft tissues to vascular beds, despite the limits due to the incomplete rotation of the tube

Recent Applications of Artificial Intelligence in Radiotherapy: Where We Are and Beyond

In recent decades, artificial intelligence (AI) tools have been applied in many medical fields, opening the possibility of finding novel solutions for managing very complex and multifactorial problems, such as those commonly encountered in radiotherapy (RT). We conducted a PubMed and Scopus search to identify the AI application field in RT limited to the last four years. In total, 1824 original papers were identified, and 921 were analyzed by considering the phase of the RT workflow according to the applied AI approaches. AI permits the processing of large quantities of information, data, and images stored in RT oncology information systems, a process that is not manageable for individuals or groups. AI allows the iterative application of complex tasks in large datasets (e.g., delineating normal tissues or finding optimal planning solutions) and might support the entire community working in the various sectors of RT, as summarized in this overview. AI-based tools are now on the roadmap for RT and have been applied to the entire workflow, mainly for segmentation, the generation of synthetic images, and outcome prediction. Several concerns were raised, including the need for harmonization while overcoming ethical, legal, and skill barriers

Improving total body irradiation with a dedicated couch and 3D-printed patient-specific lung blocks: A feasibility study

Introduction: Total body irradiation (TBI) is an important component of the conditioning regimen in patients undergoing hematopoietic stem cell transplants. TBI is used in very few patients and therefore it is generally delivered with standard linear accelerators (LINACs) and not with dedicated devices. Severe pulmonary toxicity is the most common adverse effect after TBI, and patient-specific lead blocks are used to reduce mean lung dose. In this context, online treatment setup is crucial to achieve precise positioning of the lung blocks. Therefore, in this study we aim to report our experience at generating 3D-printed patient-specific lung blocks and coupling a dedicated couch (with an integrated onboard image device) with a modern LINAC for TBI treatment. Material and methods: TBI was planned and delivered (2Gy/fraction given twice a day, over 3 days) to 15 patients. Online images, to be compared with planned digitally reconstructed radiographies, were acquired with the couch-dedicated Electronic Portal Imaging Device (EPID) panel and imported in the iView software using a homemade Graphical User Interface (GUI). In vivo dosimetry, using Metal-Oxide Field-Effect Transistors (MOSFETs), was used to assess the setup reproducibility in both supine and prone positions. Results: 3D printing of lung blocks was feasible for all planned patients using a stereolithography 3D printer with a build volume of 14.5×14.5×17.5 cm3. The number of required pre-TBI EPID-images generally decreases after the first fraction. In patient-specific quality assurance, the difference between measured and calculated dose was generally<2%. The MOSFET measurements reproducibility along each treatment and patient was 2.7%, in average. Conclusion: The TBI technique was successfully implemented, demonstrating that our approach is feasible, flexible, and cost-effective. The use of 3D-printed patient-specific lung blocks have the potential to personalize TBI treatment and to refine the shape of the blocks before delivery, making them extremely versatile

Outcome Prediction for SARS-CoV-2 Patients Using Machine Learning Modeling of Clinical, Radiological, and Radiomic Features Derived from Chest CT Images

Featured Application The present study demonstrates that semi-automatic segmentation enables the identification of regions of interest affected by SARS-CoV-2 infection for the extraction of prognostic features from chest CT scans without suffering from the inter-operator variability typical of segmentation, hence offering a valuable and informative second opinion. Machine Learning methods allow identification of the prognostic features potentially reusable for the early detection and management of other similar diseases. (1) Background: Chest Computed Tomography (CT) has been proposed as a non-invasive method for confirming the diagnosis of SARS-CoV-2 patients using radiomic features (RFs) and baseline clinical data. The performance of Machine Learning (ML) methods using RFs derived from semi-automatically segmented lungs in chest CT images was investigated regarding the ability to predict the mortality of SARS-CoV-2 patients. (2) Methods: A total of 179 RFs extracted from 436 chest CT images of SARS-CoV-2 patients, and 8 clinical and 6 radiological variables, were used to train and evaluate three ML methods (Least Absolute Shrinkage and Selection Operator [LASSO] regularized regression, Random Forest Classifier [RFC], and the Fully connected Neural Network [FcNN]) for their ability to predict mortality using the Area Under the Curve (AUC) of Receiver Operator characteristic (ROC) Curves. These three groups of variables were used separately and together as input for constructing and comparing the final performance of ML models. (3) Results: All the ML models using only RFs achieved an informative level regarding predictive ability, outperforming radiological assessment, without however reaching the performance obtained with ML based on clinical variables. The LASSO regularized regression and the FcNN performed equally, both being superior to the RFC. (4) Conclusions: Radiomic features based on semi-automatically segmented CT images and ML approaches can aid in identifying patients with a high risk of mortality, allowing a fast, objective, and generalizable method for improving prognostic assessment by providing a second expert opinion that outperforms human evaluation

PSMA PET for the Evaluation of Liver Metastases in Castration-Resistant Prostate Cancer Patients: A Multicenter Retrospective Study

Simple Summary Visceral involvement in prostate cancer (PCa) represents a negative prognostic factor. Liver metastases typically occur in systemic, late-stage, castration-resistant prostate cancer (CRPC). The diagnostic performance of [68Ga]Ga-PSMA-11-PET for visceral metastases of CRPC patients has never been systematically assessed. Our aim was to evaluate the diagnostic performance of PSMA-PET compared to conventional imaging, i.e., CT or MRI, or liver biopsy in the detection of liver metastases in CRPC patients. The secondary aim was to assess the ability of radiomics to predict the presence of liver metastases. Regarding liver metastases assessment in CRPC patients, [68Ga]-PSMA-11-PET demonstrated moderate sensitivity while high specificity, positive predictive value, and reproducibility compared to conventional imaging and liver biopsy. However, nuclear medicine physicians should carefully assess the liver parenchyma on PET images, especially in patients at higher risk for liver metastases and with high PSA values. Moreover, radiomic features may aid in recognizing higher-risk patients to develop them. Background: To evaluate the diagnostic performance of PSMA-PET compared to conventional imaging/liver biopsy in the detection of liver metastases in CRPC patients. Moreover, we evaluated a PSMA-PET/CT-based radiomic model able to identify liver metastases. Methods: Multicenter retrospective study enrolling patients with the following inclusion criteria: (a) proven CRPC patients, (b) PSMA-PET and conventional imaging/liver biopsy performed in a 6 months timeframe, (c) no therapy changes between PSMA-PET and conventional imaging/liver biopsy. PSMA-PET sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for liver metastases were calculated. After the extraction of radiomic features, a prediction model for liver metastases identification was developed. Results: Sixty CRPC patients were enrolled. Within 6 months before or after PSMA-PET, conventional imaging and liver biopsy identified 24/60 (40%) patients with liver metastases. PSMA-PET sensitivity, specificity, PPV, NPV, and accuracy for liver metastases were 0.58, 0.92, 0.82, 0.77, and 0.78, respectively. Either number of liver metastases and the maximum lesion diameter were significantly associated with the presence of a positive PSMA-PET (p < 0.05). On multivariate regression analysis, the radiomic feature-based model combining sphericity, and the moment of inverse difference (Idm), had an AUC of 0.807 (95% CI:0.686-0.920). Conclusion: For liver metastases assessment, [68Ga]Ga-PSMA-11-PET demonstrated moderate sensitivity while high specificity, PPV, and inter-reader agreement compared to conventional imaging/liver biopsy in CRPC patients

Brain perfusion imaging techniques

In questo lavoro si sono analizzate due diverse tecniche di imaging di perfusione implementate in Risonanza Magnetica e Tomografia Assiale Computerizzata (TAC). La prima analisi proposta riguarda la tecnica di Arterial Spin Labeling che permette di ottenere informazioni di perfusione senza la somministrazione di un mezzo di contrasto. In questo lavoro si è sviluppata e testata una pipeline completa, attraverso lo sviluppo sia di un protocollo di acquisizione che di post-processing. In particolare, sono stati definiti parametri di acquisizione standard, che permettono di ottenere una buona qualità dei dati, successivamente elaborati attraverso un protocollo di post processing che, a partire dall'acquisizione di un esperimento di ASL, permette il calcolo di una mappa quantitativa di cerebral blood flow (CBF). Nel corso del lavoro, si è notata una asimmetria nella valutazione della perfusione, non giustificata dai dati e probabilmente dovuta ad una configurazione hardware non ottimale. Risolta questa difficoltà tecnica, la pipeline sviluppata sarà utilizzata come standard per l’acquisizione e il post-processing di dati ASL. La seconda analisi riguarda dati acquisiti attraverso esperimenti di perfusione TAC. Si è presa in considerazione la sua applicazione a casi di infarti cerebrali in cui le tecniche di trombectomia sono risultate inefficaci. L'obiettivo di questo lavoro è stata la definizione di una pipeline che permetta il calcolo autonomo delle mappe di perfusione e la standardizzazione della trattazione dei dati. In particolare, la pipeline permette l’analisi di dati di perfusione attraverso l’utilizzo di soli software open-source, contrapponendosi alla metodologia operativa comunemente utilizzata in clinica e rendendo le analisi riproducibili. Il lavoro proposto è inserito in un progetto più ampio, che include future analisi longitudinali con coorti di pazienti più ampie per definire e validare parametri predittivi degli outcome dei pazienti

LASSO-Cox Modeling of Survival Using High-Resolution CT-Based Radiomic Features in a Cohort of COVID-19 Patients and Its Generalizability to Standard Image Reconstruction

Background: Few studies have focused on predicting the overall survival (OS) of patients affected by SARS-CoV-2 (i.e., COVID-19) using radiomic features (RFs) extracted from computer tomography (CT) images. Reconstruction of CT scans might potentially affect the values of RFs. Methods: Out of 435 patients, 239 had the scans reconstructed with a single modality, and hence, were used for training/testing, and 196 were reconstructed with two modalities were used as validation to evaluate RFs robustness to reconstruction. During training, the dataset was split into train/test using a 70/30 proportion, randomizing the procedure 100 times to obtain 100 different models. In all cases, RFs were normalized using the z-score and then given as input into a Cox proportional-hazards model regularized with the Least Absolute Shrinkage and Selection Operator (LASSO-Cox), used for feature selection and developing a robust model. The RFs retained multiple times in the models were also included in a final LASSO-Cox for developing the predictive model. Thus, we conducted sensitivity analysis increasing the number of retained RFs with an occurrence cut-off from 11% to 60%. The Bayesian information criterion (BIC) was used to identify the cut-off to build the optimal model. Results: The best BIC value indicated 45% as the optimal occurrence cut-off, resulting in five RFs used for generating the final LASSO-Cox. All the Kaplan-Meier curves of training and validation datasets were statistically significant in identifying patients with good and poor prognoses, irrespective of CT reconstruction. Conclusions: The final LASSO-Cox model maintained its predictive ability for predicting the OS in COVID-19 patients irrespective of CT reconstruction algorithms

How the Rigid and Deformable Image Registration Approaches Affect the Absorbed Dose Estimation Using Images Collected before and after Transarterial Radioembolization with ⁹⁰Y Resin Microspheres in a Clinical Setting

Background: Transarterial radioembolization (TARE) relies on directly injected 90Y- or 166Ho-loaded microspheres in the hepatic arteries. The activity to be injected is generally based on pre-TARE 99mTc-macro-aggregated-albumin (MAA) imaging, while the actual dose distribution is based on post-treatment images. The volume of interest (VOIs) propagation methods (i.e., rigid and deformable) from pre- to post-TARE imaging might affect the estimation of the mean absorbed dose in the tumor and non-tumoral liver (NTL), i.e., DT and DNTL, respectively. Methods: In 101 consecutive patients, liver and tumor were delineated on pre-TARE images and semi-automatically transferred on 90Y-PET/CT images with a rigid or deformable registration approach. Pre- and post-TARE volumes and DT/DNTL/DL were compared using correlation coefficient (CC) indexes, such as intra-class (ICC), Pearson’s (PCC), concordance (CCCo) and Bland–Altman analyses. The Kaplan–Meier curves of overall survival (OS) were calculated according to DT. Results: All computed CCs indicated very good (>0.92) agreement for volume comparison, while they suggested good (ICC ≥ 0.869, PCC ≥ 0.876 and CCCo ≥ 0.790) and moderate agreement in the intra- and inter-modality DT/DNTL/DL comparisons, respectively. Bland–Altman analyses showed percentage differences between the manual and deformable approaches of up to about −31%, 9% and 62% for tumoral volumes, DT and DNTL, respectively. The overall survival analysis showed statistically significant differences using DT cutoffs of 110, 90 and 85 Gy for the manual, rigid and deformable approaches, respectively. Conclusions: The semi-automatic transfer of VOIs from pre- and post-TARE imaging is feasible, but the selected method might affect prognostic DT/DNTL constraints

Outcome Prediction for SARS-CoV-2 Patients Using Machine Learning Modeling of Clinical, Radiological, and Radiomic Features Derived from Chest CT Images

(1) Background: Chest Computed Tomography (CT) has been proposed as a non-invasive method for confirming the diagnosis of SARS-CoV-2 patients using radiomic features (RFs) and baseline clinical data. The performance of Machine Learning (ML) methods using RFs derived from semi-automatically segmented lungs in chest CT images was investigated regarding the ability to predict the mortality of SARS-CoV-2 patients. (2) Methods: A total of 179 RFs extracted from 436 chest CT images of SARS-CoV-2 patients, and 8 clinical and 6 radiological variables, were used to train and evaluate three ML methods (Least Absolute Shrinkage and Selection Operator [LASSO] regularized regression, Random Forest Classifier [RFC], and the Fully connected Neural Network [FcNN]) for their ability to predict mortality using the Area Under the Curve (AUC) of Receiver Operator characteristic (ROC) Curves. These three groups of variables were used separately and together as input for constructing and comparing the final performance of ML models. (3) Results: All the ML models using only RFs achieved an informative level regarding predictive ability, outperforming radiological assessment, without however reaching the performance obtained with ML based on clinical variables. The LASSO regularized regression and the FcNN performed equally, both being superior to the RFC. (4) Conclusions: Radiomic features based on semi-automatically segmented CT images and ML approaches can aid in identifying patients with a high risk of mortality, allowing a fast, objective, and generalizable method for improving prognostic assessment by providing a second expert opinion that outperforms human evaluation

PVA-Microbubbles as a Radioembolization Platform: Formulation and the In Vitro Proof of Concept

This proof-of-concept study lays the foundations for the development of a delivery strategy for radioactive lanthanides, such as Yttrium-90, against recurrent glioblastoma. Our appealing hypothesis is that by taking advantage of the combination of biocompatible polyvinyl alcohol (PVA) microbubbles (MBs) and endovascular radiopharmaceutical infusion, a minimally invasive selective radioembolization can be achieved, which can lead to personalized treatments limiting off-target toxicities for the normal brain. The results show the successful formulation strategy that turns the ultrasound contrast PVA-shelled microbubbles into a microdevice, exhibiting good loading efficiency of Yttrium cargo by complexation with a bifunctional chelator. The selective targeting of Yttrium-loaded MBs on the glioblastoma-associated tumor endothelial cells can be unlocked by the biorecognition between the overexpressed αVβ3 integrin and the ligand Cyclo(Arg-Gly-Asp-D-Phe-Lys) at the PVA microbubble surface. Hence, we show the suitability of PVA MBs as selective Y-microdevices for in situ injection via the smallest (i.e., 1.2F) neurointerventional microcatheter available on the market and the accumulation of PVA MBs on the HUVEC cell line model of integrin overexpression, thereby providing ~6 × 10−15 moles of Y90 per HUVEC cell. We further discuss the potential impact of using such versatile PVA MBs as a new therapeutic chance for treating glioblastoma multiforme recurrence